The investigation of genetic factors that determine differential drug
response is a key goal of pharmacogenomics (PGX), and relies on the
often untested assumption that differential response is heritable.
While limitations in traditional study design often prohibit
heritability estimates in PGX, new approaches may allow such
estimates.  We demonstrate an in vitro model system to determine the
heritability of drug-induced cell killing and performed genome-wide
analysis for gene mapping.  The cytotoxic effect of 29 diverse
chemotherapeutic agents on lymphoblastoid cell lines (LCLs) derived
from family and population based cohorts was investigated.  We used a
high throughput format to determine cytotoxicity of the drugs on LCLs
and developed  a new evolutionary computation approach to fit response
curves for each individual.  Variance components analysis determined
the heritability for each drug response and a wide range of values was
observed across drugs.  Genome wide analysis was performed using new
analytical approaches.  These results lay the groundwork for future
studies to uncover genes influencing chemotherapeutic response.